While vaccinations against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus disease-19 (COVID-19), are underway, news of virus mutations, or variants, is causing significant anxiety and stress. Should we be alarmed? How widely have these variants spread and do they cause more severe illness? Will current therapies and new vaccines work against them? Can they be detected by viral tests? We have many questions and unfortunately, very few definitive answers at this point. Let’s take a look at how and why these virus mutations occur and the status of the primary variants that have been identified to date.
How and Why Do Viruses Mutate?
The terms mutation, variant, and strain are often used interchangeably; however, they have slight nuances (Lauring & Hodcroft, 2021). A mutation refers to the actual change in the DNA sequence of genetic material in the wild type, or original virus that occurred in nature. For example, in the Variant of Concern (VOC) 202012/01 found in the United Kingdom, a mutation occurred in the receptor binding domain (RBD) of the spike protein at position 501, where the amino acid asparagine (N) was replaced with tyrosine (Y) (Centers for Disease Control and Prevention [CDC], 2021a). In the D614G mutation, the amino acid aspartate (D) was replaced by glycine (G) at the 614
th amino-acid position of the spike protein. By the end of 2020, scientists had identified over 12,000 mutations in SARS-CoV-2 genomes (Callaway, 2020). Variants refer to a specific region of the genome which differs between two genomes. A variant is a strain when it has a different phenotype or physical property, such as a difference in antigenicity, transmissibility, or virulence (Lauring & Hodcroft, 2021).
Essentially, all viruses mutate. Viruses reproduce when they infect cells and utilize the host to make copies of itself. Viruses such as influenza and SARS-CoV-2 encode their genome in RNA which typically have higher mutation rates than DNA viruses (Lauring & Hodcroft, 2021). Coronaviruses tend to develop fewer mutations than other RNA viruses since they contain enzymes that correct some errors created during replication (Callaway, 2020). A SARS-CoV-2 virus usually experiences two single-letter mutations to its genome per month which is about half the rate as influenza. Often times, the copying mistakes are insignificant, however, when the virus infects millions of people around the world, the probability increases that one of these mistakes can have a critical impact, either making the virus less harmful or rendering it more dangerous (Hogan, 2021). A change to the SARS-CoV-2 spike protein could improve its ability to enter cells or it might alter the appearance of the virus so that prior antibodies from previous infection or a vaccine would not recognize it.
Major consequences of variants include (CDC, 2021a):
- Increased transmissibility and ability to spread faster
- Altered disease severity, either milder or more serious
- Lower detection by viral diagnostic tests, however most reverse-transcriptase polymerase chain reaction (RT-PCR) tests utilize a variety of targets and can detect the virus despite the presence of mutations
- Reduced response to treatments and medications currently used to treat COVID-19
- Improved ability to evade natural or vaccine-induced immunity
Natural selection and adaptation may play a role in determining which variants or strains become dominant as in those that develop competitive advantages such as increased transmissibility or the ability to evade immunity (Lauring & Hodcroft, 2021). The D614G mutation in the spike glycoprotein of SARS-CoV-2, which helps the virus penetrate cells, was first identified in early March 2020 and spread globally over the next month, quickly becoming the dominant strain. Researchers found that the G mutation infected cells up to 10 times more efficiently than D viruses (Calloway, 2020). Lineage B.1.1.7 (or 501UY.V1) is another variant that is swiftly spreading in the southern United Kingdom and as of late 2020, accounted for almost 30% of all COVID-19 infections in England. According to Dr. Anthony Fauci (CNN, 2021), the only way to prevent variants from becoming dominant is to stop them from spreading by following public health guidelines and vaccinating as many people as possible.
Will the Vaccines Work Against These Variants?
Since vaccines and natural infection create a response that targets multiple segments of the spike protein or the entire spike protein, the virus would need several mutations to avoid natural or vaccine-induced immunity (Lauring & Hodcroft, 2021). In addition, major vaccine manufacturers feel that they will be able to modify their vaccines as needed to combat these potential variants, however this is a lengthy and costly process (Hogan, 2021). As of the writing of this article, researcher have found that currently authorized vaccines are able to recognize these variants (CDC, 2021b).
The following is a summary of the primary variants that have been identified to date.
COVID-19 Variants |
Variant Details |
Mutation |
Comments |
D614G polymorphism
Origin: Uncertain; documented in late January/early February 2020
Detected in U.S.?
Yes |
D614G: glycine (G) replaced aspartic acid (D) substitution at the 614th amino acid position |
- June 2020: it replaced the original strain to become the dominant form globally.
- Increased infectivity and transmission but does not cause more severe illness or impact the effectiveness of lab tests, therapies, vaccines or public health prevention measures.
|
B.1.1.7 lineage
(Also known as
VOC 202012/01)
Origin: Unknown; appeared in United Kingdom in September 2020
Detected in U.S.?
Yes, December 2020 |
Contains over a dozen mutations, including eight on the RBD of the spike protein (N501Y), 69/70 deletion and P681H
|
- Highly transmissible
- May be associated with increased disease severity compared to other variants, although data is still pending
|
B.1.351 lineage
(Also known as
20H/501Y.V2)
Origin: South Africa, October 2020
Detected in U.S.?
Yes, January 2021 |
Spike protein mutations: K417N, E484K, N501Y |
- Increased transmissibility
- No evidence of increased disease severity
|
P.1 lineage
(Also known as 20J/501Y.V3)
Origin: Brazil
Detected in U.S.?
Yes, January 2021 |
Contains 17 unique mutations including three in the spike protein RBD: K417T, E484K, N501Y |
|
[Reference: CDC, 2021a; World Health Organization (WHO), 2020]
We are learning more and more about the SARS-CoV-2 variants every day but until we have achieved
widespread vaccination, individuals should continue to practice
physical distancing, good hand hygiene, wear a mask, keep rooms well ventilated, avoid crowds, and cough into a bent elbow or tissue (WHO, 2021).
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